1. Field of the Invention
This invention relates to enrichment of analytes in liquid sample analysis.
2. Description of the Related Art
In a range of multidimensional analytical techniques, the presence of non-analyte, matrix-related substances required for one analytical dimension often interfere with another dimension, and in these circumstances it is desirable to remove non-analytes from the analytical stream flowing from an upstream analytical dimension before the stream is introduced to a subsequent downstream analytical dimension in the scheme. In particular, for example, for liquid phase based separation techniques, it is desirable to remove non-analyte(s) from the analytical stream in an on-line flow-through manner without compromising the analytical procedure.
In liquid phase separation techniques, such as High Performance Liquid Chromagraphy ("HPLC"), mixtures are separated from each other spatially, volumetrically and temporally in a flowing stream. The resolution of such a system is based on the separation between the mean of the concentration profile for two peaks relative to the standard deviation of the concentration profile of each of the peaks. The separation process itself introduces an increase in the variance of the concentration profile. However, further increase in the variance (also known as band broadening, peak broadening or dispersion) is introduced as the analyte peaks pass through extra-column "dead-volume" such as connecting tubes, detector flow cells and mixing chamber. Particularly for modern miniaturized chromatography systems, this extra dispersion can be unacceptable and steps are taken to minimize it.
In mass spectrometry ("MS") where electrospray ionization is employed, introduction of non-volatile salts into the electrospray ion source leads to diminished performance. Accordingly, contamination of a sample stream from a liquid chromatography ("LC") column by non-volatile salts effectively precludes the use of ion exchange chromatography as a separation technique in analytical systems in which liquid chromatography is coupled with mass spectrometry ("LC/MS").
Electrodialytic treatment may be employed for isolation and enrichment of compounds from complex solutions. Publications of interest with respect to sample treatment using electrodialysis or electrofiltration include: A. J. J. Debets et al. (1992), Journal of Chromatography, Vol. 600, pp. 163-173; A. J. J. Debets, et al. (1990), Chromatographia, Vol. 30, No. 7/8, pp. 361-366; A. J. J. Debets, et al. (1994), Chromatographia, Vol. 39, No. 7/8, pp. 460-468; M. W. Lada, et al. (1995), Analytica Chemica Acta, Vol. 307, pp. 217-225; E. Jacobs, et al. (1986), Analytical Biochemistry, Vol. 154, pp. 583-589; W. R. Bowen (1991), "Electrically Driven Membrane Process", in Chromatographic and Membrane Processes in Biotechnology, C. A. Costa and J. S. Cabral, eds., Kluwer Academic Publishers, Dordrecht, Netherlands, pp. 207 to 221 (review); K. Takahashi et al. (1995), Journal of Chemical Engineering of Japan, Vol. 28, No. 2, pp. 154-158; T. -C. Huang et al. (1993), Chemical Engineering Communications, Vol. 122, pp. 213-225; U. Gobel et al. (1987), Journal of Biochemical and Biophysical Methods, Vol. 14, pp. 245-260; M. Bier et al. (1990), Separation Science and Technology, Vol. 25, Nos. 9/10, pp. 997-1005; E. Sommerfeld et al., German patent publication 2,340,362; N. B. Egen, et al. U.S. Pat No. 5,336,387; J. -I. Liao, et al. U.S. Pat. No. 5,480,526; S. M. Jain, U.S. Pat. No. 4,441,978; R. Oertli, U.S. Pat. No. 4,576,696; J. M. Goldstein, U.S. Pat. No. 4,614,576; W. A. McRae, U.S. Pat. No. 4,146,455 and 4,180,451; and S. B. Tuwiner, U.S. Pat. No. 3,674,669.
Additional publications and patents of interest include U.S. Pat. No. 5,082,548 and U.S. Pat. No. 5,055,399; and N. Hese et al., German patent publication 3,337,668.
All articles, references, standards, patents, patent applications and the like referred to herein are hereby incorporated herein by reference in their entirety.